Agrin Protein, Rat (HEK293, His)

Agrin protein is a heparan sulfate basal lamina glycoprotein that has a crucial role in the formation and maintenance of the neuromuscular junction (NMJ), as well as in directing key events in postsynaptic differentiation. Specifically, the neuron-specific (z+) isoform of Agrin is a component of the AGRN-LRP4 receptor complex, which activates and phosphorylates MUSK, thereby inducing NMJ formation. This process involves the regulation of various processes, including the transcription of specific genes and the clustering of AChR in the postsynaptic membrane, with calcium ions playing a critical role in AChR clustering. The neuronal function of Agrin is tightly regulated by alternative splicing, glycan binding, and proteolytic processing. In addition to its role in NMJ formation, Agrin also modulates calcium ion homeostasis in neurons by increasing cytoplasmic calcium ion levels. In the central nervous system (CNS), Agrin functions by inhibiting the alpha(3)-subtype of Na+/K+-ATPase and inducing depolarization at CNS synapses. The transmembrane isoform of Agrin, known as TM-agrin, is predominantly expressed in brain neurons and promotes dendritic filopodia and synapse formation in mature hippocampal neurons, primarily through the action of attached glycosaminoglycan chains and Rho-family GTPases. Multiple isoforms of Agrin, including isoform 1, isoform 4, isoform 5, and isoform 6, contain neuron-specific C-terminal insertions and are potent activators of AChR clustering. Isoform 5, known as agrin (z+8), which contains an 8-AA insertion, forms a receptor complex with the neuronal AGRN, muscle-specific kinase MUSK, and LRP4. The splicing factors NOVA1 and NOVA2 regulate the splicing of Agrin and the production of the 'z' isoforms.